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Bioactive Materials May 2024Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current...
Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.
PubMed: 38390528
DOI: 10.1016/j.bioactmat.2024.02.016 -
Nature Oct 2023Transposable elements are genomic parasites that expand within and spread between genomes. PIWI proteins control transposon activity, notably in the germline. These...
Transposable elements are genomic parasites that expand within and spread between genomes. PIWI proteins control transposon activity, notably in the germline. These proteins recognize their targets through small RNA co-factors named PIWI-interacting RNAs (piRNAs), making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. Although the processing of piRNA precursors is an essential step in this process, many of the molecular details remain unclear. Here, we identify an endoribonuclease, precursor of 21U RNA 5'-end cleavage holoenzyme (PUCH), that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain proteins (SLFL proteins), executes 5'-end piRNA precursor cleavage. PUCH-mediated processing strictly requires a 7-methyl-G cap (mG-cap) and a uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds to piRNA precursors, and that this interaction enhances piRNA production in vivo. The identification of PUCH concludes the search for the 5'-end piRNA biogenesis factor in C. elegans and uncovers a type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (SLFN) genes have been associated with immunity, exposing a molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.
Topics: Animals; Argonaute Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA Transposable Elements; Endoribonucleases; Holoenzymes; Piwi-Interacting RNA; RNA Cap Analogs
PubMed: 37758951
DOI: 10.1038/s41586-023-06588-2 -
ACS Applied Materials & Interfaces Aug 2023The maskless and chemical-free conversion and patterning of synthetic polymer precursors into laser-induced graphene (LIG) via laser-induced pyrolysis is a relatively... (Review)
Review
The maskless and chemical-free conversion and patterning of synthetic polymer precursors into laser-induced graphene (LIG) via laser-induced pyrolysis is a relatively new but growing field. Bioderived precursors from lignocellulosic materials can also be converted to LIG, opening a path to sustainable and environmentally friendly applications. This review is designed as a starting point for researchers who are not familiar with LIG and/or who wish to switch to sustainable bioderived precursors for their applications. Bioderived precursors are described, and their performances (mainly crystallinity and sheet resistance of the obtained LIG) are compared. The three main fields of application are reviewed: supercapacitors and electrochemical and physical sensors. The key advantages and disadvantages of each precursor for each application are discussed and compared to those of a benchmark of polymer-derived LIG. LIG from bioderived precursors can match, or even outperform, its synthetic analogue and represents a viable and sometimes better alternative, also considering its low cost and biodegradability.
PubMed: 37471123
DOI: 10.1021/acsami.3c07687 -
World Journal of Clinical Cases Jun 2024The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly...
The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly disease. Premalignant lesions such as Intraductal Papillary Mucinous Neoplasms or Mucinous Cystic Neoplasms of the pancreas are detectable on imaging exams and this permits their management prior their invasive development. Pancreatic intraepithelial neoplasms (PanIN) are the most frequent precursors of pancreatic adenocarcinoma (PDAC), and its particular type PanIN high-grade represents the malignant non-invasive form of PDAC. Unfortunately, PanINs are not detectable on radiologic exams. Nevertheless, they can associate indirect imaging signs which would rise the diagnostic suspicion. When this suspicion is established, the patient will be enrolled in a follow-up strategy that includes performing of blood test and serial imaging test such as computed tomography or magnetic resonance imaging, which will cost in the best-case scenario a burden of healthcare systems, and potential mortality in the worst-case scenario when the patient underwent resection surgery, worthless when there is no moderate or high grade dysplasia in the final histopathology. This issue will be avoid having at its disposal a diagnostic technique capable of detecting high-grade PanIN lesions, such is the cytology of pancreatic juice obtained by nasopancreatic intubation. Herein, we review the possibility of detection of early malignant lesions before they become invasive PADC.
PubMed: 38898835
DOI: 10.12998/wjcc.v12.i17.2935 -
Genes Oct 2023Since the discovery of RNA splicing as a fundamental step to remove introns from pre-mRNA to produce mature mRNAs, substantial research in the past decades has...
Since the discovery of RNA splicing as a fundamental step to remove introns from pre-mRNA to produce mature mRNAs, substantial research in the past decades has highlighted RNA splicing as a critical mediator of gene expression and proteome diversity, also being important in many developmental and biological processes [...].
Topics: Humans; RNA Splicing; RNA Precursors; Neoplasms; RNA, Messenger; Introns
PubMed: 38002963
DOI: 10.3390/genes14112020 -
Nature Communications Oct 2023Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury....
Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery.
Topics: Mice; Animals; Lateral Ventricles; Neural Stem Cells; Vascular Endothelial Growth Factor A; Neurogenesis; Stroke
PubMed: 37816732
DOI: 10.1038/s41467-023-42138-0 -
Science Advances Sep 2023Measurable residual disease (MRD), defined as the population of cancer cells that persist following therapy, serves as the critical reservoir for disease relapse in...
Measurable residual disease (MRD), defined as the population of cancer cells that persist following therapy, serves as the critical reservoir for disease relapse in acute myeloid leukemia and other malignancies. Understanding the biology enabling MRD clones to resist therapy is necessary to guide the development of more effective curative treatments. Discriminating between residual leukemic clones, preleukemic clones, and normal precursors remains a challenge with current MRD tools. Here, we developed a single-cell MRD (scMRD) assay by combining flow cytometric enrichment of the targeted precursor/blast population with integrated single-cell DNA sequencing and immunophenotyping. Our scMRD assay shows high sensitivity of approximately 0.01%, deconvolutes clonal architecture, and provides clone-specific immunophenotypic data. In summary, our scMRD assay enhances MRD detection and simultaneously illuminates the clonal architecture of clonal hematopoiesis/preleukemic and leukemic cells surviving acute myeloid leukemia therapy.
Topics: Humans; Leukemia, Myeloid, Acute; Biological Assay; Flow Cytometry; Genotype; Immunophenotyping
PubMed: 37729414
DOI: 10.1126/sciadv.adg0488 -
Synthetic and Systems Biotechnology Dec 2023The microbial synthesis of paclitaxel is attractive for its short-cycle, cost-effectiveness, and sustainability. However, low paclitaxel productivity, depleted capacity... (Review)
Review
The microbial synthesis of paclitaxel is attractive for its short-cycle, cost-effectiveness, and sustainability. However, low paclitaxel productivity, depleted capacity during subculture and storage, and unclear biosynthesis mechanisms restrain industrial microbial synthesis. Along with the isolation of various paclitaxel-producing microorganisms and the development of versatile molecular tools, tremendous promises for microbial paclitaxel synthesis have become increasingly prominent. In this review, we summarize the progress of microbial synthesis of paclitaxel in recent years, focusing on paclitaxel-producing endophytes and representative engineering microorganism hosts that were used as chassis for paclitaxel precursor synthesis. Numerous wide-type microbes can manufacture paclitaxel, and fermentation process optimization and strain improvement can greatly enhance the productivity. Engineered microbes can efficiently synthesize precursors of paclitaxel by introducing exogenous synthetic pathway. Mining paclitaxel synthetic pathways and genetic manipulation of endophytes will accelerate the construction of microbial cell factories, indefinitely contributing to paclitaxel mass production by microbes. This review emphasizes the potential and provides solutions for efficient microbial paclitaxel mass production.
PubMed: 37954482
DOI: 10.1016/j.synbio.2023.10.002 -
Frontiers in Plant Science 2023Phytosulfokines (PSKs) are a class of disulfated pentapeptides and are regarded as plant peptide hormones. PSK-α, -γ, -δ, and -ϵ are four bioactive PSKs that are... (Review)
Review
Phytosulfokines (PSKs) are a class of disulfated pentapeptides and are regarded as plant peptide hormones. PSK-α, -γ, -δ, and -ϵ are four bioactive PSKs that are reported to have roles in plant growth, development, and immunity. In this review, we summarize recent advances in PSK biosynthesis, signaling, and function. PSKs are encoded by precursor genes that are widespread in higher plants. PSKs maturation from these precursors requires a sulfation step, which is catalyzed by a tyrosylprotein sulfotransferase, as well as proteolytic cleavage by subtilisin serine proteases. PSK signaling is mediated by plasma membrane-localized receptors PSKRs that belong to the leucine-rich repeat receptor-like kinase family. Moreover, multiple biological functions can be attributed to PSKs, including promoting cell division and cell growth, regulating plant reproduction, inducing somatic embryogenesis, enhancing legume nodulation, and regulating plant resistance to biotic and abiotic stress. Finally, we propose several research directions in this field. This review provides important insights into PSKs that will facilitate biotechnological development and PSK application in agriculture.
PubMed: 38250441
DOI: 10.3389/fpls.2023.1326964